Measurement of blood-brain barrier permeability in acute ischemic stroke using standard first-pass perfusion CT data

Abstract

Background and purpose: Increased blood-brain barrier permeability is believed to be associated with complications following acute ischemic stroke and with infarct expansion. Measurement of blood-brain barrier permeability requires a delayed image acquisition methodology, which prolongs examination time, increasing the likelihood of movement artefacts and radiation dose. Existing quantitative methods overestimate blood-brain barrier permeability when early phase CT perfusion data are used. The purpose of this study is to develop a method that yields the correct blood-brain barrier permeability value using first-pass perfusion CT data.

Methods: We acquired 43 CT perfusion datasets, comprising experimental (n = 30) and validation subject groups (n = 13). The Gjedde-Patlak method was used to estimate blood-brain barrier permeability using first-pass (30-60 s after contrast administration) and delayed phase (30-200 s) data. In the experimental group, linear regression was used to obtain a function predicting first-pass blood-brain barrier permeability estimates from delayed phase estimates in each stroke compartment. The reliability of prediction with this function was then tested using data from the validation group.

Results: The predicted delayed phase blood-brain barrier permeability was strongly correlated with the measured delayed phase value (r = 0.67 and 0.6 for experimental and validation group respectively; p < 0.01). Predicted and measured delayed phase blood-brain barrier permeability in each stroke compartment were not significantly different in both experimental and validation groups.

Conclusion: We have developed a method of estimating blood-brain barrier permeability using first-pass perfusion CT data. This predictive method allows reliable blood-brain barrier permeability estimation within standard acquisition time, minimizing the likelihood of motion artefacts thereby improving image quality and reducing radiation dose.

Keywords: Blood–brain barrier permeability; Delayed phase; First-pass; Perfusion CT.

Graphical abstract

Fig. 1

Example of Gjedde–Patlak plot in one subject using mean intensity values in the entire ischemic region and in the M1 segment of the middle cerebral artery. The slope of the plot is lower for the 60–200 s time frame than the 30–60s time frame. A better linear fit is seen for the 60–200 s time frame.

Fig. 2

Relationship between predicted K₁^DP and measured K₁^DP in all stroke compartments. Results for the experimental group are shown on the left and for the validation group on the right.

Fig. 3

Images of predicted and measured K₁^DP showing increased blood–brain barrier permeability in the ischemic region (white boundary) and infarct core (black boundary) compared to the homologous regions in the unaffected contralateral hemisphere.